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Identification by microarray analysis of aspartate aminotransferase and glutamine synthetase as glucocorticoid target genes in a mouse Schwann cell line.
J Steroid Biochem Mol Biol. 2005 Dec; 97(4):342-52.JS

Abstract

Schwann cells have been identified as targets for glucocorticoids. Besides genes implicated in the myelination process, the target genes of glucocorticoids have not been identified in these cells. For that purpose, we performed microarray analysis on MSC80 (mouse Schwann cells) treated with a synthetic glucocorticoid, dexamethasone. These cells express a functional glucocorticoid receptor (GR), but none of the other steroid receptors. This allowed us to identify genes specifically regulated by GR in the absence of the mineralocorticoid receptor. Among the 5000 genes analyzed, 12 were at least two-fold upregulated and 91 genes were at least two-fold down-regulated upon treatment with dexamethasone. Because of their potential role in Schwann cell homeostasis, we selected, for further analysis, the upregulated genes encoding glutamine synthetase (GS) and cytosolic aspartate aminotransferase (cAspAT). These genes play a crucial role in the glutamate cycle which was shown to be vital in neuron-astrocyte cross-talk in the central nervous system. Their activation was confirmed by semi-quantitative and real-time PCR. A detailed analysis of cAspAT promoter activity revealed that the mechanism of regulation by GR in Schwann cells differs from that in hepatoma cells, suggesting a cell-specific regulation. The transactivation potency of the two Glucocorticoid Responsive Units (GRU) present in the cAspAT promoter seems to be dependent on the levels of the GR in MSC80 cells. Furthermore, we show that an increase in GR levels under certain circumstances could considerably potentiate the effects of glucocorticoids on the cAspAT promoter via synergistic activation of both GRU, To the opposite, an enhancement in GR levels did not further potentiate Dex-activation of the GS promoter, showing a differential mechanism of action of GR in the context of both promoters.

Authors+Show Affiliations

Inserm UMR488, Faculté de Médecine Paris-Sud, 80, Rue du Général Leclerc, 94276 Le Kremlin-Bicêtre, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16182522

Citation

Grenier, Julien, et al. "Identification By Microarray Analysis of Aspartate Aminotransferase and Glutamine Synthetase as Glucocorticoid Target Genes in a Mouse Schwann Cell Line." The Journal of Steroid Biochemistry and Molecular Biology, vol. 97, no. 4, 2005, pp. 342-52.
Grenier J, Tomkiewicz C, Trousson A, et al. Identification by microarray analysis of aspartate aminotransferase and glutamine synthetase as glucocorticoid target genes in a mouse Schwann cell line. J Steroid Biochem Mol Biol. 2005;97(4):342-52.
Grenier, J., Tomkiewicz, C., Trousson, A., Rajkowski, K. M., Schumacher, M., & Massaad, C. (2005). Identification by microarray analysis of aspartate aminotransferase and glutamine synthetase as glucocorticoid target genes in a mouse Schwann cell line. The Journal of Steroid Biochemistry and Molecular Biology, 97(4), 342-52.
Grenier J, et al. Identification By Microarray Analysis of Aspartate Aminotransferase and Glutamine Synthetase as Glucocorticoid Target Genes in a Mouse Schwann Cell Line. J Steroid Biochem Mol Biol. 2005;97(4):342-52. PubMed PMID: 16182522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification by microarray analysis of aspartate aminotransferase and glutamine synthetase as glucocorticoid target genes in a mouse Schwann cell line. AU - Grenier,Julien, AU - Tomkiewicz,Céline, AU - Trousson,Amalia, AU - Rajkowski,Krzysztof M, AU - Schumacher,Michael, AU - Massaad,Charbel, Y1 - 2005/09/22/ PY - 2004/12/03/received PY - 2005/06/21/accepted PY - 2005/9/27/pubmed PY - 2006/1/6/medline PY - 2005/9/27/entrez SP - 342 EP - 52 JF - The Journal of steroid biochemistry and molecular biology JO - J Steroid Biochem Mol Biol VL - 97 IS - 4 N2 - Schwann cells have been identified as targets for glucocorticoids. Besides genes implicated in the myelination process, the target genes of glucocorticoids have not been identified in these cells. For that purpose, we performed microarray analysis on MSC80 (mouse Schwann cells) treated with a synthetic glucocorticoid, dexamethasone. These cells express a functional glucocorticoid receptor (GR), but none of the other steroid receptors. This allowed us to identify genes specifically regulated by GR in the absence of the mineralocorticoid receptor. Among the 5000 genes analyzed, 12 were at least two-fold upregulated and 91 genes were at least two-fold down-regulated upon treatment with dexamethasone. Because of their potential role in Schwann cell homeostasis, we selected, for further analysis, the upregulated genes encoding glutamine synthetase (GS) and cytosolic aspartate aminotransferase (cAspAT). These genes play a crucial role in the glutamate cycle which was shown to be vital in neuron-astrocyte cross-talk in the central nervous system. Their activation was confirmed by semi-quantitative and real-time PCR. A detailed analysis of cAspAT promoter activity revealed that the mechanism of regulation by GR in Schwann cells differs from that in hepatoma cells, suggesting a cell-specific regulation. The transactivation potency of the two Glucocorticoid Responsive Units (GRU) present in the cAspAT promoter seems to be dependent on the levels of the GR in MSC80 cells. Furthermore, we show that an increase in GR levels under certain circumstances could considerably potentiate the effects of glucocorticoids on the cAspAT promoter via synergistic activation of both GRU, To the opposite, an enhancement in GR levels did not further potentiate Dex-activation of the GS promoter, showing a differential mechanism of action of GR in the context of both promoters. SN - 0960-0760 UR - https://www.unboundmedicine.com/medline/citation/16182522/Identification_by_microarray_analysis_of_aspartate_aminotransferase_and_glutamine_synthetase_as_glucocorticoid_target_genes_in_a_mouse_Schwann_cell_line_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960-0760(05)00338-9 DB - PRIME DP - Unbound Medicine ER -